Gastric cancer is the fourth most common form of incident cancer and the second most common cause of cancer death in the world. This malignancy is considered to be poorly treatable, and the surgery that is the mainstay of current treatment carries significant morbidity and mortality. To better treat and prevent this disease, it is important to understand factors that affect its development. p53 tumor suppressor is among the cellular factors that play an important role in the prevention of gastric tumors. Although the p53 protein has been relatively well characterized, less is known about other members of the p53 family, p73 and p63. Accumulating evidence suggest that p73 and p63 significantly affect the p53 activity and function in concert with p53 in regulation of tumorigenesis. Our data suggest that p73 plays an important role in the interaction of gastric epithelial cells with H. pylori, a Gram-negative bacterial pathogen that is a prominent risk factor for the development of gastric cancer. We aim to delineate the role of the p53 protein family in the development of gastric tumor using mouse models and other in vitro and in vivo approaches. These comprehensive studies may provide new avenues for the development of novel prognostic and therapeutic targets.